GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Myeloma Plasma Cell Dormancy - 'Eradicating The Sleeping Giant'
Funder
National Health and Medical Research Council
Funding Amount
$834,428.00
Summary
Multiple myeloma is a fatal cancer that develops in the skeleton. Current therapies are initially effective, but patients develop resistance and the disease returns. This makes the search for drugs to overcome resistance a priority. Myeloma cells can hide in bone in a dormant state where they are insensitive to chemotherapy. We have identified new drug targets in dormant cells. We are investigating whether these new targets can be used eradicate myeloma cells and cure the disease.
Precision Nanomedicine-based Diagnostics And Therapeutics For Refractory Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$7,329,484.00
Summary
The vast majority of cancer patients die of their disease due to the emergence of drug resistant cancer cells or metastatic disease that is diagnosed at late stages. Our program aims to develop new types of therapy to specifically target aggressive cancers. To detect cancer early and evaluate the effectiveness of cancer therapy, we will develop sensitive diagnostic tools and devices. This research has application to both childhood and adult cancers.
Transient Tissue ‘priming’ Via FAK Inhibition To Impair Pancreatic Cancer Progression And Improve Sensitivity To Gemcitabine/Abraxane
Funder
National Health and Medical Research Council
Funding Amount
$643,848.00
Summary
The success of cancer drugs is dependent on many factors including the properties of the tumour tissue. As a tumour grows it changes the tissue around it, and this affects response to treatment. Combining classical biology with engineering to generate 3D models that mimic tumours, along with cutting-edge imaging technology and mouse models, we will target FAK-controlled cancer cell pathways that sense tissue changes, together with already approved cancer drugs to improve patient outcome.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.
Real-time Optical Window Imaging Of AKT-FRET Biosensor Mice To Maximise PI3K/AKT Drug Targeting Within The Hypoxic Microenvironment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours with low oxygen levels known as hypoxia. Here, we will specifically target factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of AKT inhibitors in pancreatic cancer.
Biosensor Imaging In Preclinical Pancreatic Cancer Targeting: Taking Cancer Targeting To New Dimensions.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Using cutting-edge imaging technology and 3D models that mimic cancer, we can map areas of poor drug response within distinct 'stages' or regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug response in order to improve the encouraging anti-cancer profile of new or current drugs in pancreatic cancer.
PARP And PI3K Inhibition In Pancreatic Cancer: Intravital Insights And ‘fine-tune’ Priming Using AKT And Single/double-strand DNA Break Biosensor Mice.
Funder
National Health and Medical Research Council
Funding Amount
$760,505.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we can map areas of poor drug response within distinct regions of tumours with chemotherapy. Here, we will shift factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of PI3K and DNA repair inhibitors in pancreatic cancer.